Resolving spin, valley, and moir\'e quasi-angular momentum of interlayer excitons in WSe2/WS2 heterostructures

Moir\'e superlattices provide a powerful way to engineer properties of electrons and excitons in two-dimensional van der Waals heterostructures. The moir\'e effect can be especially strong for interlayer excitons, where electrons and holes reside in different layers and can be addressed separately. In particular, it was recently proposed that the moir\'e superlattice potential not only localizes interlayer exciton states at different superlattice positions, but also hosts an emerging moir\'e quasi-angular momentum (QAM) that periodically switches the optical selection rules for interlayer excitons at different moir\'e sites. Here we report the observation of multiple interlayer exciton states coexisting in a WSe2/WS2 moir\'e superlattice and unambiguously determine their spin, valley, and moir\'e QAM through novel resonant optical pump-probe spectroscopy and photoluminescence excitation spectroscopy. We demonstrate that interlayer excitons localized at different moir\'e sites can exhibit opposite optical selection rules due to the spatially-varying moir\'e QAM. Our observation reveals new opportunities to engineer interlayer exciton states and valley physics with moir\'e superlattices for optoelectronic and valleytronic applications

Soluble Human Epidermal Growth Factor Receptor 2 (sHER2) as a Potential Risk Assessment, Screening, and Diagnostic Biomarker of Lung Adenocarcinoma

Lung cancer is the leading cause of cancer-related death in the United States. Here, we evaluated the potential clinical utility of soluble human epidermal growth factor receptor 2 (sHER2) for the risk assessment, screening, and diagnosis of non-small cell lung cancer (NSCLC) using an unmatched case-control study design. Serum sHER2 concentrations were measured by immunoassay in 244 primary NSCLC cases and 218 healthy controls. Wilcoxon rank-sum tests, logistic regression models, and receiver operating characteristic plots were used to assess whether sHER2 is associated with lung cancer. Median serum sHER2 concentrations are higher in patients with adenocarcinoma than squamous cell carcinoma regardless of gender, and sHER2 is a weak, independent biomarker of adenocarcinoma, but not of squamous cell carcinoma, adjusted for age and gender. The age-adjusted relative risk (odds) of adenocarcinoma is 3.95 (95% CI: 1.22, 12.81) and 7.93 (95% CI: 2.26, 27.82) greater for women and men with high sHER2 concentrations (≥ 6.60 ng/mL) vs. low sHER2 concentrations (≤ 1.85 ng/mL), respectively. When adjusted for each other, sHER2, age, and gender discern healthy controls from patients with primary adenocarcinomas of the lung with 85.9% accuracy. We conclude that even though serum sHER2 is not a strong, stand-alone discriminatory biomarker of adenocarcinoma, sHER2 may be a useful, independent covariate in multivariate risk assessment, screening, and diagnostic models of lung cancer

Zip4 (Slc39a4) Expression is Activated in Hepatocellular Carcinomas and Functions to Repress Apoptosis, Enhance Cell Cycle and Increase Migration

Background: The zinc transporter ZIP4 (Slc39a4) is important for proper mammalian development and is an essential gene in mice. Recent studies suggest that this gene may also play a role in pancreatic cancer. Methods/Principal Findings: Herein, we present evidence that this essential zinc transporter is expressed in hepatocellular carcinomas. Zip4 mRNA and protein were dramatically elevated in hepatocytes in the majority of human hepatocellular carcinomas relative to noncancerous surrounding tissues, as well as in hepatocytes in hepatocellular carcinomas occurring in farnesoid X receptor-knockout mice. Interestingly, meta-analysis of microarray data in the Geo and Oncomine databases suggests that Zip4 mRNA may also be elevated in many types of cancer. Potential mechanisms of action of ZIP4 were examined in cultured cell lines. RNAi knockdown of Zip4 in mouse Hepa cells significantly increased apoptosis and modestly slowed progression from G0/G1 to S phase when cells were released from hydroxyurea block into zinc-deficient medium. Cell migration assays revealed that RNAi knockdown of Zip4 in Hepa cells depressed in vitro migration whereas forced over-expression in Hepa cells and MCF-7 cells enhanced in vitro migration. Conclusions: ZIP4 may play a role in the acquisition of zinc by hepatocellular carcinomas, and potentially many different cancerous cell-types, leading to repressed apoptosis, enhanced growth rate and enhanced invasive behavior

Smoking, use of smokeless tobacco, HLA genotypes and incidence of latent autoimmune diabetes in adults

Aims/hypotheses Smoking and use of smokeless tobacco (snus) are associated with an increased risk of type 2 diabetes. We investigated whether smoking and snus use increase the risk of latent autoimmune diabetes in adults (LADA) and elucidated potential interaction with HLA high-risk genotypes. Methods Analyses were based on Swedish case-control data (collected 2010-2019) with incident cases of LADA (n=593) and type 2 diabetes (n=2038), and 3036 controls, and Norwegian prospective data (collected 1984-2019) with incident cases of LADA (n=245) and type 2 diabetes (n=3726) during 1,696,503 person-years of follow-up. Pooled RRs with 95% CIs were estimated for smoking, and ORs for snus use (case-control data only). The interaction was assessed by attributable proportion (AP) due to interaction. A two-sample Mendelian randomisation (MR) study on smoking and LADA/type 2 diabetes was conducted based on summary statistics from genome-wide association studies. Results Smoking (RRpooled 1.30 [95% CI 1.06, 1.59] for current vs never) and snus use (OR 1.97 [95% CI 1.20, 3.24] for >= 15 box-years vs never use) were associated with an increased risk of LADA. Corresponding estimates for type 2 diabetes were 1.38 (95% CI 1.28, 1.49) and 1.92 (95% CI 1.27, 2.90), respectively. There was interaction between smoking and HLA high-risk genotypes (AP 0.27 [95% CI 0.01, 0.53]) in relation to LADA. The positive association between smoking and LADA/type 2 diabetes was confirmed by the MR study. Conclusions/interpretation Our findings suggest that tobacco use increases the risk of LADA and that smoking acts synergistically with genetic susceptibility in the promotion of LADA.Peer reviewe

Nonlinear Dispersion Relation and Out-of-Plane Second Harmonic Generation in MoSSe and WSSe Janus Monolayers

Janus transition metal dichalcogenides are an emerging class of atomically thin materials with engineered broken mirror symmetry that gives rise to long-lived dipolar excitons, Rashba splitting, and topologically protected solitons. They hold great promise as a versatile nonlinear optical platform due to their broadband harmonic generation tunability, ease of integration on photonic structures, and nonlinearities beyond the basal crystal plane. Here, we study second and third harmonic generation in MoSSe and WSSe Janus monolayers. We use polarization-resolved spectroscopy to map the full second-order susceptibility tensor of MoSSe, including its out-of-plane components. In addition, we measure the effective third-order susceptibility, and the second-order nonlinear dispersion close to exciton resonances for both MoSSe and WSSe at room and cryogenic temperatures. Our work sets a bedrock for understanding the nonlinear optical properties of Janus transition metal dichalcogenides and probing their use in the next-generation on-chip multifaceted photonic devices.Comment: 10 pages, 3 figures. SI: 8 pages, 5 figure

T\u3cem\u3ecf\u3c/em\u3e21 Marks Visceral Adipose Mesenchymal Progenitors and Functions as a Rate-Limiting Factor During Visceral Adipose Tissue Development

Distinct locations of different white adipose depots suggest anatomy-specific developmental regulation, a relatively understudied concept. Here, we report a population of Tcf21 lineage cells (Tcf21 LCs) present exclusively in visceral adipose tissue (VAT) that dynamically contributes to VAT development and expansion. During development, the Tcf21 lineage gives rise to adipocytes. In adult mice, Tcf21 LCs transform into a fibrotic or quiescent state. Multiomics analyses show consistent gene expression and chromatin accessibility changes in Tcf21 LC, based on which we constructed a gene-regulatory network governing Tcf21 LC activities. Furthermore, single-cell RNA sequencing (scRNA-seq) identifies the heterogeneity of Tcf21 LCs. Loss of Tcf21 promotes the adipogenesis and developmental progress of Tcf21 LCs, leading to improved metabolic health in the context of diet-induced obesity. Mechanistic studies show that the inhibitory effect of Tcf21 on adipogenesis is at least partially mediated via Dlk1 expression accentuation

Progenitor Cell Isolation From Mouse Epididymal Adipose Tissue and Sequencing Library Construction

Here, we present a protocol to isolate progenitor cells from mouse epididymal visceral adipose tissue and construct bulk RNA and assay for transposase-accessible chromatin with sequencing (ATAC-seq) libraries. We describe steps for adipose tissue collection, cell isolation, and cell staining and sorting. We then detail procedures for both ATAC-seq and RNA sequencing library construction. This protocol can also be applied to other tissues and cell types directly or with minor modifications. For complete details on the use and execution of this protocol, please refer to Liu et al. (2023).1 *1 Liu, Q., Li, C., Deng, B., Gao, P., Wang, L., Li, Y., ... & Fu, X. (2023). Tcf21 marks visceral adipose mesenchymal progenitors and functions as a rate-limiting factor during visceral adipose tissue development. Cell reports, 42(3) 112166. https://doi.org/10.1016/j.celrep.2023.11216